Xu Hui, Qi Guobao, Li Kunpeng, Yang Keshi, Luo Dawei, Cai Zhongxu
Department of Spinal Surgery, Liaocheng People's Hospital, No. 67, Dongchang Xilu Road, 252000, Liaocheng, Shandong, China.
Department of Spinal Surgery, Dongying People's Hospital, No. 317, Nanyi Road, 257091, Dongying, Shandong, China.
J Inflamm (Lond). 2021 Feb 2;18(1):6. doi: 10.1186/s12950-021-00273-9.
Intervertebral disk degeneration (IVDD) contributes to low back pain. Increased cell apoptosis and inflammation, decreased extracellular matrix are associated with IVDD. Nuclear factor-kappa B (NF-κB) signaling pathway and inflammatory cytokines are implicated in the pathophysiology of IVDD.
In present study, we established a mechanical stretching stress-stimulated nucleus pulposus (NP) cell model. We knocked down NF-κB p65 by siRNA transfection to inhibit NF-κB and evaluated the effects of NF-κB inhibition on intervertebral disk degeneration. We applied the mechanical stretching stress on NP cells and inhibited NF-κB by siRNA, then evaluated the expression of inflammatory cytokines, matrix metalloproteinase (MMP), aggrecan, collagen II, and monitored viability and apoptosis of NP cells.
Mechanical stretching stress induced the expression of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while inhibited the production of aggrecan and collagen II in NP cells. Mechanical stretching stress decreased the cell viability and induced apoptosis in NP cells. Inhibition of NF-κB by siRNA suppressed the production of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while upregulated the expression of aggrecan and collagen II in NP cells.
Inhibition of NF-κB by knocking down p65 suppressed over-mechanical stretching stress-induced cell apoptosis and promoted viability in NP cell. Inhibition of NF-κB suppressed inflammation and degeneration of NP cells in IVDD.
椎间盘退变（IVDD）会导致腰痛。细胞凋亡增加、炎症反应增强以及细胞外基质减少与IVDD相关。核因子-κB（NF-κB）信号通路和炎性细胞因子参与了IVDD的病理生理过程。
在本研究中，我们建立了机械拉伸应力刺激的髓核（NP）细胞模型。我们通过小干扰RNA（siRNA）转染敲低NF-κB p65以抑制NF-κB，并评估NF-κB抑制对椎间盘退变的影响。我们对NP细胞施加机械拉伸应力并通过siRNA抑制NF-κB，然后评估炎性细胞因子、基质金属蛋白酶（MMP）、聚集蛋白聚糖、胶原蛋白II的表达，并监测NP细胞的活力和凋亡情况。
机械拉伸应力诱导NP细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、NF-κB、MMP-3和MMP-13的表达，同时抑制聚集蛋白聚糖和胶原蛋白II的产生。机械拉伸应力降低了NP细胞的活力并诱导其凋亡。通过siRNA抑制NF-κB可抑制NP细胞中TNF-α、IL-1β、NF-κB、MMP-3和MMP-13的产生，同时上调聚集蛋白聚糖和胶原蛋白II的表达。
通过敲低p65抑制NF-κB可抑制过度机械拉伸应力诱导的NP细胞凋亡并促进其活力。抑制NF-κB可抑制IVDD中NP细胞的炎症和退变。
